BACKGROUND:Finasteride, an inhibitor of 5 α-reductase (Type II), lowers intraprostatic dihydrotestosterone (DHT), which is reflected in serum as reduced 5α-androstane-3α,17β-diol glucuronide (3 -dG).
It also modestly increases serum testosterone (T), estrone (E1) and estradiol (E2). In this altered hormonal milieu, it is unknown whether serum concentrations of these hormones are associated with prostate cancer risk.
METHODS:In this nested case-control study of men in the finasteride arm of the Prostate Cancer Prevention Trial, sex steroid hormones and sex hormone binding globulin (SHBG) were measured at baseline and approximately 3-years post-treatment in 553 prostate cancer cases and 694 controls.
RESULTS:Median post-treatment changes in concentrations of 3 -dG, T, E1, and E2 were -73.8%, +10.1%, +11.2%, and +7.5% (all p< 0.001), respectively. Neither the pre- nor post-treatment concentrations of 3 -dG, nor its change, were associated with risk. Pre-treatment, high concentrations of E1 and low concentrations of T were associated with increased cancer risk (Odds Ratio[95% CI] quartile 4 vs 1: 1.38[0.99-1.93] ptrend=0.03; 0.64 [0.43-0.93] ptrend=0.07, respectively). Post-treatment, high concentrations of both E1 and E2 and were associated with increased cancer risk (OR[95% CI] quartile 4 vs 1: 1.54[1.09-2.17] ptrend=0.03; 1.49[1.07-2.07] ptrend=0.02, respectively).
CONCLUSIONS: Among finasteride-treated men, concentrations of 3 -dG were not associated with total or Gleason grades 2-6, 7-10 or 8-10 cancer. High serum estrogens may increase cancer risk when intraprostatic DHT is pharmacologically lowered. IMPACT. Low post-treatment serum estrogens may identify men more likely to benefit from use of finasteride to prevent prostate cancer.
Written by:
Kristal AR, Till CA, Tangen CM, Goodman PJ, Neuhouser ML, Stanczyk FZ, Chu LW, Patel SK, Thompson IM Jr, Reichardt J, Hoque AM, Platz EA, Figg WD, van Bokhoven A, Lippman SM, Hsing AW. Are you the author?
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M4-B402, PO Box 19024, Seattle, WA, 98109-1024, United States.
Reference: Cancer Epidemiol Biomarkers Prev. 2012 Aug 9. Epub ahead of print.
doi: 10.1158/1055-9965.EPI-12-0695
PubMed Abstract
PMID: 22879203
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